Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups

NCT07523022 | Enrolling By Invitation Phase 4

• 1 other identifier: NNGYK943
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Men enrolled in the study are assigned to each APHRODITE group. Group 2,3,4 are treated with either gonadotropin preparations or clompihene-citrate (except group 4). The type of the treatment (gonadotropin vs clomiphene) is randomized. After treatment, hormonal measurements, spermiogram and DNA fragmentation tests are repeated, allowing for analysis of the outcome.

Conditions

Male Infertility

Keywords

APHRODITE classification; male infertility; gonadotropin therapy; clomiphene-citrate

Outcome Measures

Primary Outcomes (6)

• sperm DNA fragmentation

  sperm DNA fragmentation Index (%), high DNA stainability (%) are measured and compared to the pretreatment values. Lower numbers mean improvement in this outcome.

  12 weeks of treatment

• ejaculate volume

  ejaculate volume (ml) after treatment are assessed and compared to the pretreatment values. Higher number means improvement in this outcome.

  12 weeks of treatment

• sperm concentration

  Sperm concentrations (million/ml) before and after the treatment are compared. Higher number means improvement in this outcome.

  12 weeks

• sperm motility

  Sperm total motility (%), progressive motility (%) after the treatment are compared to the pretreatment values. Higher numbers mean improvement in this outcome.

  12 weeks

• total sperm count, total functional sperm count

  Total sperm count (million) = ejaculate volume (ml) x sperm concentration (million/ml) and total functional sperm count (million) = total sperm count x progressive motility x 100 are compared before and after the treatment. Higher numbers mean improvement in this outcome.

  12 weeks

• Sperm morphology

  Percent of normal sperm morphology (%) is counted after the treatment and compared to the pretreatment result. Higher number mean improvement in this outcome.

  12 weeks

Secondary Outcomes (4)

• gonadotropin vs clomiphene - total sperm count, total functional sperm count

  12 weeks of treatment

• gonadotropin vs clomiphene - DNA fragmentation

  12 weeks

• Gonadotropin vs clomiphene - sperm total motility, progressive motility

  12 weeks

• gonadotropin vs clomiphene - normal sperm morphology

  12 weeks

Other Outcomes (3)

• Gonadotropin hormones

  12 weeks of treatment

• Testosterone level

  12 weeks

• Estradiol level

  12 weeks

Study Arms (5)

APHRODITE category 2 treated with gonadotropin

EXPERIMENTAL

subcutaneous recFSH 3x150NE weekly for 12 weeks

Drug: recFSH

APHRODITE category 2 treated with clomiphene-citrate

EXPERIMENTAL

per os 50mg clomiphene-citrate daily for 12 weeks

Drug: Clomiphene Citrate 50 mg

APHRODITE category 3 treated with gonadotropin

EXPERIMENTAL

subcutaneous recFSH 3x150NE weekly and subcutaneous hCG 2x5000NE weekly for 12 weeks

Drug: recFSH; Drug: HCG injection

APHRODITE category 3 treated with clomiphene-citrate

EXPERIMENTAL

per os 50mg clomiphene-citrate daily for 12 weeks

Drug: Clomiphene Citrate 50 mg

APHRODITE category 4 treated with gonadotropin

EXPERIMENTAL

subcutaneous hCG 2x5000NE weekly for 12 weeks, if FSH level drops below 1.5 IU/l, subcutaneous recFSH 3x150NE weekly added

Drug: recFSH; Drug: HCG injection

Interventions

HCG injection DRUG

hCG 2x5000NE sc weekly for 12 weeks

Also known as: human chorionic gonadotropin, choriogonadotropin alfa

APHRODITE category 3 treated with gonadotropin; APHRODITE category 4 treated with gonadotropin

recFSH DRUG

recFSH 3x150NE sc weekly for 12 weeks

Also known as: recombinant FSH

APHRODITE category 2 treated with gonadotropin; APHRODITE category 3 treated with gonadotropin; APHRODITE category 4 treated with gonadotropin

Clomiphene Citrate 50 mg DRUG

clompihene-citrate 50mg p.o. daily for 12 weeks

Also known as: CC

APHRODITE category 2 treated with clomiphene-citrate; APHRODITE category 3 treated with clomiphene-citrate

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• abnormal sperm analysis result, APHRODITE 2,3,4 categories

You may not qualify if:

• obstructive azoospermia
• non-obstructive azoospermia due to genetical defects (Klinefelter-syndrome, AZFa, AZFb microdeletion syndrome etc)
• problems with the administration of subcutaneous injections
• disagreement

Sponsors & Collaborators

• Szeged University: lead

Study Sites (1)

Reproductive Medicine Centre, Department of Obstetrics and Gynecology, University of Szeged

Szeged, 6724, Hungary

Location

MeSH Terms

Conditions

Infertility, Male

Interventions

Chorionic Gonadotropin; Clomiphene

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Norbert Pásztor, MD, PhD

  University of Szeged, Department of Obstetrics and Gynecology, Reproductive Medicine Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: The sperm analysis after the treatment is performed by a biologist, who is masked about the type of the treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: March 28, 2026
• First Posted: April 13, 2026
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Starting after publication
• Access Criteria: Researchers upon request by email (hirt78@gmail.com)

Locations

HU (1)